The C-076 compounds are a series of compounds which are isolated from the fermentation broth of Streptomyces avermitilis. The morphological characteristics of the culture, as well as the fermentation methods and processes of isolation of the C-076 compounds is described in the West German published patent Application Ser. No. 27,170,407.
The C-076 compounds have the following structure: ##STR1## wherein R is the 4'-(.alpha.-L-oleandrosyl)-.alpha.-L-oleandrose group of the structure: ##STR2## and wherein the broken line indicates a single or double bond;
R.sub.1 is hydroxy and is present only when said broken line indicates a single bond;
R.sub.2 is iso-propyl or sec-butyl; and
R.sub.3 is methoxy or hydroxy.
There are eight different C-076 compounds and they are given the designations A1a, A1b, A2a, A2b, B1a, B1b, B2a, B2b, based upon the structure of the individual compounds.
With reference to the R.sub.1, R.sub.2 and R.sub.3 groups of the above structural formula, the individual C-076 compounds are as set forth below:
______________________________________ R.sub.1 R.sub.2 R.sub.3 ______________________________________ A1a Double Bond sec-butyl OCH.sub.3 A1b Double Bond iso-propyl OCH.sub.3 A2a OH sec-butyl OCH.sub.3 A2b OH iso-propyl OCH.sub.3 B1a Double Bond sec-butyl OH B1b Double Bond iso-propyl OH B2a OH sec-butyl OH B2b OH iso-propyl OH ______________________________________
The C-076 compounds are generally isolated as mixtures of a and b components. Such compounds differ only in the nature of the R.sub.2 substituent and the minor structural differences have been found to have very little effect on the isolation procedures, chemical reactivity and biological activity of such compounds.
In addition, derivatives of the C-076 compounds have been prepared. In particular, the 22,23-dihydro derivatives of the 1-series of compounds have been found to have particularly advantageous biological properties. The 22,23-dihydro derivatives are prepared by selectively hydrogenating the 22,23 unsaturated precursor. That is such compounds are prepared from the C-076 A1a/A1b and C-076 B1a/B1b pair of compounds. The 22,23 dihydro compounds and their preparation are described in European published patent application Serial No. 8300435.1. This, of course, requires that the C-076 A1a/A1b and B1a/B1b pairs be separated from the A2a/A2b and B2a/B2b pairs of compounds, and then reduced to prepare the dihydro derivatives. The main problem encountered with this procedure is that the A2a/A2b and B2a/B2b compounds remain unused, and in effect wasted.
The process of the instant invention removes this waste by converting the unused compounds into the 22,23-unsaturated precursors of the biologically preferred compounds, or into the even more biologically preferred 22,23-dihydro derivatives.